Figure 1.

Schematic mechanism of chromothripsis. The first step of chromothripsis is the generation of clustered DNA double-strand breaks. Chromothripsis may involve one or a few chromosomes, a chromosomal arm (both p and q arms), or an entire chromosome. This results in multiple fragments that are stitched together in a random order and orientation by DNA repair machineries. During this process, some of the fragments may be lost. The derivative chromosome(s) will contain complex structural rearrangements. By piecing together all the structural variants detected by paired-end or mate-pair sequencing, it should be possible to delineate the derivative chromosomes.